Physical activity plays a profound role in tissue anabolism. Yet, surprisingly little is understood about the mechanisms that link exercise with growth and development in children and adolescents. The broad aim of this work is to understand the unique interaction of two distinct biological processes, human development and physical exercise, each of which is characterized by tissue plasticity. The general hypothesis is that endurance exercise training can modulate tissue growth by functional increases in growth hormone (GH) and/or by increased bioavailability of the insulin-like growth factors (IGF-I and II). The GH effect may be mediated by: 1) acute increases in GH following brief exercise; 2) increases in the frequency or amplitude of spontaneous GH pulses consequent to training; and/or 3) training effects on circulating GH binding protein (BP) suggesting alteration in GH tissue receptors. The IGF effects may be mediated by GH-related increases in circulating IGFs and/or by increased circulating IGF resulting from an exercise-associated IGFBP proteolysis. It is additionally hypothesized that the GH and IGF mechanisms that link physical activity and tissue growth are profoundly influenced by diet, gender, and maturational state. Studies will be done in pre- and late pubertal children and in adults using diet intervention, exercise training programs, magnetic resonance techniques, mathematical modeling of breath-to-breath measurements of gas exchange, stable isotope assessment of energy expenditure, and state-of-the-art assessments of circulating growth factors and their binding proteins. The health enhancing role of exercise is noted in Healthy People 2000, as is the need to promote physical fitness for all Americans. This proposal addresses four critical areas. 1. The Unique Biology of Physical Activity during Childhood--Few other voluntary activities can exert as profound and widespread stimulus for anabolic adaptation of tissues as does exercise. 2. The Role of Exercise During Childhood in Preventing Disease Later in Life--This research will, hopefully, identify those patterns of physical activity that optimize cardiorespiratory development as children grow. 3. The Increasing Use of Growth Factors in Disease--Understanding normal growth factor responses to exercise and diet is essential for determining the clinical use of such agents in children with acute or chronic diseases. 4. The Therapeutic Use of Exercise in Children with Chronic Lung and Heart Diseases. Guidelines designed to maximize the anabolic effects of exercise in children with chronic heart and lung diseases do not exist. This research may provide a biologic bases for the use of exercise as a rehabilitation tool in children.